Risks of second primary cancers among 584,965 female and male breast cancer survivors in England: a 25-year retrospective cohort study.

Background: Second primary cancers (SPCs) after breast cancer (BC) present an increasing public health burden, with little existing research on socio-demographic, tumour, and treatment effects. We addressed this in the largest BC survivor cohort to date, using a novel linkage of National Disease Registration Service datasets. Methods: The cohort included 581,403 female and 3562 male BC survivors diagnosed between 1995 and 2019. We estimated standardized incidence ratios (SIRs) for combined and site-specific SPCs using incidences for England, overall and by age at BC and socioeconomic status. We estimated incidences and Kaplan-Meier cumulative risks stratified by age at BC, and assessed risk variation by socio-demographic, tumour, and treatment characteristics using Cox regression. Findings: Both genders were at elevated contralateral breast (SIR: 2.02 (95% CI: 1.99-2.06) females; 55.4 (35.5-82.4) males) and non-breast (1.10 (1.09-1.11) females, 1.10 (1.00-1.20) males) SPC risks. Non-breast SPC risks were higher for females younger at BC diagnosis (SIR: 1.34 (1.31-1.38) <50 y, 1.07 (1.06-1.09) ≥50 y) and more socioeconomically deprived (SIR: 1.00 (0.98-1.02) least deprived quintile, 1.34 (1.30-1.37) most). Interpretation: Enhanced SPC surveillance may benefit BC survivors, although specific recommendations require more detailed multifactorial risk and cost-benefit analyses. The associations between deprivation and SPC risks could provide clinical management insights. Funding: CRUK Catalyst Award CanGene-CanVar (C61296/A27223). Cancer Research UK grant: PPRPGM-Nov 20∖100,002. This work was supported by core funding from the NIHR Cambridge Biomedical Research Centre (NIHR203312)]. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.

Feasibility of comparing medical management and surgery (with neurosurgery or stereotactic radiosurgery) with medical management alone in people with symptomatic brain cavernoma - protocol for the Cavernomas: A Randomised Effectiveness (CARE) pilot trial.

INTRODUCTION: The top research priority for cavernoma, identified by a James Lind Alliance Priority setting partnership was 'Does treatment (with neurosurgery or stereotactic radiosurgery) or no treatment improve outcome for people diagnosed with a cavernoma?' This pilot randomised controlled trial (RCT) aims to determine the feasibility of answering this question in a main phase RCT. METHODS AND ANALYSIS: We will perform a pilot phase, parallel group, pragmatic RCT involving approximately 60 children or adults with mental capacity, resident in the UK or Ireland, with an unresected symptomatic brain cavernoma. Participants will be randomised by web-based randomisation 1:1 to treatment with medical management and with surgery (neurosurgery or stereotactic radiosurgery) versus medical management alone, stratified by prerandomisation preference for type of surgery. In addition to 13 feasibility outcomes, the primary clinical outcome is symptomatic intracranial haemorrhage or new persistent/progressive focal neurological deficit measured at 6 monthly intervals. An integrated QuinteT Recruitment Intervention (QRI) evaluates screening logs, audio recordings of recruitment discussions, and interviews with recruiters and patients/parents/carers to identify and address barriers to participation. A Patient Advisory Group has codesigned the study and will oversee its progress. ETHICS AND DISSEMINATION: This study was approved by the Yorkshire and The Humber-Leeds East Research Ethics Committee (21/YH/0046). We will submit manuscripts to peer-reviewed journals, describing the findings of the QRI and the Cavernomas: A Randomised Evaluation (CARE) pilot trial. We will present at national specialty meetings. We will disseminate a plain English summary of the findings of the CARE pilot trial to participants and public audiences with input from, and acknowledgement of, the Patient Advisory Group. TRIAL REGISTRATION NUMBER: ISRCTN41647111.

Primary retroperitoneal sarcoma: A comparison of survival outcomes in specialist and non-specialist sarcoma centres.

BACKGROUND: Consensus guidelines outline that patients with primary retroperitoneal sarcoma (RPS) should be managed within specialist sarcoma centres (SSC). There is, however, a paucity of population-based data detailing incidence and outcomes in these patients. Hence, we aimed to evaluate patterns of care among RPS patients in England and compare outcomes for those undergoing surgery in high-volume specialist sarcoma centres (HV-SSC), low-volume SSC (LV-SSC), and non-SSC (N-SSC). METHODS: Data on patients diagnosed with primary RPS between 2013 and 2018 were extracted from NHS Digital's National Cancer Registration and Analysis Service using the national cancer registration dataset. Diagnostic pathways, treatment, and survival outcomes were compared between HV-SSC, LV-SSC, and N-SSC. Uni- and multivariate analyses were calculated. RESULTS: Of 1878 patients diagnosed with RPS, 1120 (60%) underwent surgery within 12 months of diagnosis, with 847 (76%) operated on at SSC; of these, 432 patients (51%) were operated on in HV-SSC, and 415 (49%) in LV-SSC. One- and 5-year estimated overall survival (OS) rates for patients undergoing surgery in N-SSC were 70.6% (95% confidence interval [CI]: 64.8-75.7) and 42.0% (CI: 35.9-47.9), compared to 85.0% (CI: 81.1-88.1) and 51.7% (CI: 46.6-56.6) in LV-SSC (p < 0.01), and 87.4% (CI: 83.9-90.2) and 62.8% (CI: 57.9-67.4) in HV-SSC, (p < 0.01). After adjusting for patient- and treatment-related factors, patients treated in HV-SSC were found to have significantly longer OS than those treated at LV-SSC, with an adjusted hazard ratio of 0.78 (CI: 0.62-0.96, p < 0.05). CONCLUSION: Patients with RPS undergoing surgery in HV-SSC have significantly better survival outcomes than those treated in N-SSC and L-SSC.

Generation of a thermostable, oral Zika vaccine that protects against virus challenge in non-human primates.

Here we report the development of a thermally stable, orally administered, candidate Zika vaccine using human serotype 5 adenovirus (AdHu5). We engineered AdHu5 to express the genes for the envelope and NS1 proteins of Zika virus. AdHu5 was formulated using a proprietary platform, OraPro, comprising a mix of sugars and modified amino acids that can overcome elevated temperatures (37 C), and an enteric coated capsule that protects the integrity of the AdHu5 from the acid in the stomach. This enables the delivery AdHu5 to the immune system of the small intestine. We show that oral delivery of AdHu5 elicited antigen-specific serum IgG immune responses in a mouse model and in a non-human primate model. Importantly, these immune responses were able reduce viral counts in mice and to prevent detectable viraemia in the non-human primates on challenge with live Zika virus. This candidate vaccine has significant advantages over many current vaccines that are maintained in a cold or ultra-cold chain and require parenteral administration.

Risk of Aneurysm Rupture (ROAR) study: protocol for a long-term, longitudinal, UK multicentre study of unruptured intracranial aneurysms.

INTRODUCTION: Unruptured intracranial aneurysms (UIA) are common in the adult population, but only a relatively small proportion will rupture. It is therefore essential to have accurate estimates of rupture risk to target treatment towards those who stand to benefit and avoid exposing patients to the risks of unnecessary treatment. The best available UIA natural history data are the PHASES study. However, this has never been validated and given the known heterogeneity in the populations, methods and biases of the constituent studies, there is a need to do so. There are also many potential predictors not considered in PHASES that require evaluation, and the estimated rupture risk is largely based on short-term follow-up (mostly 1 year). The aims of this study are to: (1) test the accuracy of PHASES in a UK population, (2) evaluate additional predictors of rupture and (3) assess long-term UIA rupture rates. METHODS AND ANALYSIS: The Risk of Aneurysm Rupture study is a longitudinal multicentre study that will identify patients with known UIA seen in neurosurgery units. Patients will have baseline demographics and aneurysm characteristics collected by their neurosurgery unit and then a single aggregated national cohort will be linked to databases of hospital admissions and deaths to identify all patients who may have subsequently suffered a subarachnoid haemorrhage. All matched admissions and deaths will be checked against medical records to confirm the diagnosis of aneurysmal subarachnoid haemorrhage. The target sample size is 20 000 patients. The primary outcome will be aneurysm rupture resulting in hospital admission or death. Cox regression models will be built to test each of the study's aims. ETHICS AND DISSEMINATION: Ethical approval has been given by South Central Hampshire A Research Ethics Committee (21SC0064) and Confidentiality Advisory Group support (21CAG0033) provided under Section 251 of the NHS Act 2006. The results will be disseminated in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN17658526.

Incidence and survival of soft tissue sarcoma in England between 2013 and 2017, an analysis from the National Cancer Registration and Analysis Service.

There is a paucity of population-based data detailing the incidence and survival of patients with soft tissue sarcoma (STS), in part due to the heterogeneity of disease and changes to classification. Here, the incidence and survival of all STS subtypes registered in England between 2013 and 2017 were analysed using cancer registry data held by the National Cancer Registration and Analysis Service. Age-standardised incidence rates were calculated per 1 000 000 using the 2013 European Standard Population. Net survival was computed using Brenner's alternative method, with the Ederer II estimator. Age-specific overall survival was assessed using Kaplan-Meier. The influence of age, sex, socioeconomic deprivation and diagnostic routes on survival was assessed using Cox proportional hazards modelling. In total, 19 717 patients were diagnosed with STS, an average of 3943 patients per year and representing approximately 0.8% of malignancies. The most common histological diagnoses were Gastrointestinal Stromal Tumours (GIST), leiomyosarcoma and undifferentiated sarcoma, accounting for 20.2%, 13.3% and 12.7% of all sarcomas, respectively. Five-year net survival for all malignant STS was 65.0%; and was lowest for patients with vascular tumours at 39%. Patients from most deprived cohorts had 23% greater chance of dying within 5 years than patients in least deprived areas. This population-based study has allowed us for the first time to define the incidence and survival rates of prevalent STS subtypes in England such as GIST, liposarcoma and leiomyosarcoma, as well as rare entities and groups with inferior outcome. This data is invaluable for service provision, benchmarking and addressing inequality.

Radiological follow-up of endovascularly treated intracranial aneurysms: a survey of current practice in the UK and Ireland.

PURPOSE: Due to the risk of intracranial aneurysm (IA) recurrence and the potential requirement for re-treatment following endovascular treatment (EVT), radiological follow-up of these aneurysms is necessary. There is little evidence to guide the duration and frequency of this follow-up. The aim of this study was to establish the current practice in neurosurgical units in the UK and Ireland. METHODS: A survey was designed with input from interventional neuroradiologists and neurosurgeons. Neurovascular consultants in each of the 30 neurosurgical units providing a neurovascular service in the UK and Ireland were contacted and asked to respond to questions regarding the follow-up practice for IA treated with EVT in their department. RESULTS: Responses were obtained from 28/30 (94%) of departments. There was evidence of wide variations in the duration and frequency of follow-up, with a minimum follow-up duration for ruptured IA that varied from 18 months in 5/28 (18%) units to 5 years in 11/28 (39%) of units. Young patient age, previous subarachnoid haemorrhage and incomplete IA occlusion were cited as factors that would prompt more intensive surveillance, although larger and broad-necked IA were not followed-up more closely in the majority of departments. CONCLUSIONS: There is a wide variation in the radiological follow-up of IA treated with EVT in the UK and Ireland. Further standardisation of this aspect of patient care is likely to be beneficial, but further evidence on the behaviour of IA following EVT is required in order to inform this process.

A survey of the radiological follow-up of unruptured intracranial aneurysms in the United Kingdom.

OBJECTIVE: Unruptured intracranial aneurysms (UIA) are common. For many the treatment risks outweigh their risk of subarachnoid haemorrhage and patients undergo surveillance imaging. There is little data to inform if and how to monitor UIAs resulting in widely varying practices. This study aimed to determine the current practice of unruptured UIA surveillance in the United Kingdom. METHODS: A questionnaire was designed to address the themes of surveillance protocols for UIA including when surveillance is initiated, how frequently it is performed, and when it is terminated. Additionally, how aneurysm growth is managed and how clinically meaningful growth is defined were explored. The questionnaire was distributed to members of the British Neurovascular Group using probability-based cluster and non-probability purposive sampling methods. RESULTS: Responses were received from 30 of the 30 (100.0%) adult neurosurgical units in the United Kingdom of which 27 (90.0%) routinely perform surveillance for aneurysm growth. Only four units had a unit policy. The mean patient age up to which a unit would initiate follow-up of a low-risk UIA was 65.4 ± 9.0 years. The time points at which imaging is performed varied widely. There was an even split between whether units use a fixed duration of follow-up or an age threshold for terminating surveillance. Forty percent of units will follow-up patients more than 5 years from diagnosis. The magnitude in the change in size that was felt to constitute growth ranged from 1 to 3mm. No units routinely used vessel wall imaging although 27 had access to 3T MRI capable of performing it. CONCLUSIONS: There is marked heterogeneity in surveillance practices between units in the United Kingdom. This study will help units better understand their practice relative to their peers and provide a framework forplanning further research on aneurysm growth.

Incidence, prevalence and survival in patients with Langerhans cell histiocytosis: A national registry study from England, 2013-2019.

This analysis is the largest population-based study to date to provide contemporary and comprehensive epidemiological estimates of all third edition of the International Classification of Diseases for Oncology (ICD-O-3) coded Langerhans cell histiocytosis (LCH) from England. People of all ages were identified from the National Cancer Registration Dataset using ICD-O-3 morphologies 9751-9754 for neoplasms diagnosed in 2013-2019. A total of 658 patients were identified, of whom 324 (49%) were children aged <15 years. The age-standardised incidence rate was 4.46 (95% confidence interval [CI] 3.99-4.98) per million children and 1.06 (95% CI 0.94-1.18) per million adults aged ≥15 years. Prevalence of LCH was 9.95 (95% CI 9.14-10.81) per million persons at the end of 2019. The 1-year overall survival (OS) was 99% (95% CI 97%-100%) for children and 90% (95% CI 87%-93%) for adults. Those aged ≥60 years had poorer OS than those aged <15 years (hazard ratio [HR] 22.12, 95% CI 7.10-68.94; p < 0.001). People in deprived areas had lower OS than those in the least deprived areas (HR 5.36, 95% CI 1.16-24.87; p = 0.03). There will inevitably be other environmental factors and associations yet to be identified, and the continued standardised data collection will allow further evaluation of data over time. This will be increasingly important with developments in LCH management following the large collaborative international trials such as LCH IV.

National Health Service interventions in England to improve care to Armed Forces veterans.

Armed Forces veterans (AFVs) are first and foremost citizens of the UK and are therefore-like all UK residents-entitled to universal healthcare, free at the point of need. This means that AFVs have nearly all their healthcare needs met by the NHS, which provides access to a full range of generic services. However, since 2013 there has been an Armed Forces team that can also support veterans. This review is an assessment of the work of this group over the last eight years. The health needs of AFVs have been investigated and are not significantly different from those of their demographically matched peers. However, due to their demographics, selection at recruitment and their roles, AFVs compared with the general population are more likely to be male, white and old and have fewer pre-existing or hereditary conditions. However, they do suffer from higher rates of musculoskeletal injury, different patterns of mental health illness and have historically been higher users-and abusers-of alcohol and tobacco. In addition to supporting mainstream services used by AFVs, the NHS in England commissions a bespoke range-specific 'Priority' NHS services such as those for mental health or for rehabilitation of veterans using prostheses. New interventions are continuing to be developed to improve AFVs' healthcare and are aligned to the NHS Long Term Plan and the restoration and recovery plans after the COVID-19 pandemic.

Dual-Antigen COVID-19 Vaccine Subcutaneous Prime Delivery With Oral Boosts Protects NHP Against SARS-CoV-2 Challenge.

We have developed a dual-antigen COVID-19 vaccine incorporating genes for a modified SARS-CoV-2 spike protein (S-Fusion) and the viral nucleocapsid (N) protein with an Enhanced T-cell Stimulation Domain (N-ETSD) to increase the potential for MHC class II responses. The vaccine antigens are delivered by a human adenovirus serotype 5 platform, hAd5 [E1-, E2b-, E3-], previously demonstrated to be effective in the presence of Ad immunity. Vaccination of rhesus macaques with the hAd5 S-Fusion + N-ETSD vaccine by subcutaneous prime injection followed by two oral boosts elicited neutralizing anti-S IgG and T helper cell 1-biased T-cell responses to both S and N that protected the upper and lower respiratory tracts from high titer (1 x 106 TCID50) SARS-CoV-2 challenge. Notably, viral replication was inhibited within 24 hours of challenge in both lung and nasal passages, becoming undetectable within 7 days post-challenge.

Comparison of Navigated versus Fluoroscopic-Guided Pedicle Screw Placement Accuracy and Complication Rate.

OBJECTIVES: Accurate placement of the pedicle screw is requisite for any successful spinal instrumentation procedure. Screw insertion can be achieved using free-hand and fluoroscopic- or navigation-guided techniques. We sought to assess the variation in accuracy between fluoroscopic- and navigation-guided techniques, which are both used in Sheffield Teaching Hospitals National Health Service Trust, a tertiary spine referral center. METHODS: Using a retrospective study design, we assessed all the pedicle screws placed between 2013 and 2018. Radiographic and clinical assessment of all cases was performed. RESULTS: We studied 176 spinal instrumented cases, with a total of 831 screws implanted, out of which 296 (35.6%) were navigated and 535 (64.4%) were fluoroscopic guided. Pathology treated included spinal stenosis, spondylolisthesis, tumors, and trauma. Suboptimal screw position was identified in 2.03% (n = 6) of the navigation-guided series and 4.11% (n = 22) of the fluoroscopic-guided series with an overall screw misplacement rate of 3.4%. Evaluating surgeons' individual accuracy rates revealed that suboptimal screw placement registered a higher variation for the fluoroscopy-guided technique, and the misplacement rate was higher for surgeons with a lower volume of cases. CONCLUSIONS: Use of navigation during spinal instrumentation helps lower the rate of screw misplacement for spinal surgeons who are at the beginning of their learning curve or do not frequently perform this kind of procedure. Navigation-guided spinal instrumentation is more accurate compared with fluoroscopic-guided techniques and appears to have a lower complication rate.

Spinal manipulation for the management of cervicogenic headache: A systematic review and meta-analysis.

BACKGROUND: Spinal manipulative therapy (SMT) is frequently used to manage cervicogenic headache (CGHA). No meta-analysis has investigated the effectiveness of SMT exclusively for CGHA. OBJECTIVE: To evaluate the effectiveness of SMT for CGHA. DATABASES AND DATA TREATMENT: Five databases identified randomized controlled trials comparing SMT with other manual therapies. The PEDro scale assessed the risk-of-bias. Pain and disability data were extracted and converted to a common scale. A random effects model was used for several follow-up periods. GRADE described the quality of evidence. RESULTS: Seven trials were eligible. At short-term follow-up, there was a significant, small effect favouring SMT for pain intensity (mean difference [MD] -10.88 [95% CI, -17.94, -3.82]) and small effects for pain frequency (standardized mean difference [SMD] -0.35 [95% CI, -0.66, -0.04]). There was no effect for pain duration (SMD - 0.08 [95% CI, -0.47, 0.32]). There was a significant, small effect favouring SMT for disability (MD - 13.31 [95% CI, -18.07, -8.56]). At intermediate follow-up, there was no significant effects for pain intensity (MD - 9.77 [-24.21 to 4.68]) and a significant, small effect favouring SMT for pain frequency (SMD - 0.32 [-0.63 to - 0.00]). At long-term follow-up, there was no significant effects for pain intensity (MD - 0.76 [-5.89 to 4.37]) and for pain frequency (SMD - 0.37 [-0.84 to 0.10]). CONCLUSION: For CGHA, SMT provides small, superior short-term benefits for pain intensity, frequency and disability, but not pain duration, however, high-quality evidence in this field is lacking. The long-term impact is not significant. SIGNIFICANCE: CGHA are a common headache disorder. SMT can be considered an effective treatment modality, with this review suggesting it providing superior, small, short-term effects for pain intensity, frequency and disability when compared with other manual therapies. These findings may help clinicians in practice better understand the treatment effects of SMT alone for CGHA.

Transarterial CT angiography for surgical planning of spinal dural arteriovenous fistula.

OBJECTIVE: We report a novel method to provide excellent anatomical depiction of a dural arteriovenous fistula (dAVF) for surgical planning. METHODS: A 78-year-old female presented with progressive back pain, deteriorating mobility and urinary incontinence with a background of obesity and severe osteoarthritis. Initial MRI suspected dAVF and subsequent spinal angiography encountered an extremely tortuous and arteriosclerotic aorta, hence catheterisation of the segmental-intercostal and lumbar vessels proved challenging. Contrast injection into the aortic arch via a pigtail catheter for arterial-phase CT angiogram of the descending aorta was performed. RESULTS: This modality of imaging delineated the dAVF showing extensive involvement of the whole spine accounting for the patient's symptoms. Furthermore this allowed characterisation of bony anatomy in relation to the fistula facilitating precise surgical approach. The dAVF was successfully disconnected through a localised laminectomy centred over the lesion. CONCLUSION: This specific technique for dAVF characterisation has not been previously reported, although trans-venous angiography has been used to some effect. In view of diagnostic and therapeutic technical difficulties that are often faced in such patients, this technique may be a useful alternative that is not only helpful in accurate diagnosis but helps in providing an invaluable guide for the surgical approach. ADVANCES IN KNOWLEDGE: This case highlights the difficulties that one may be faced within cases of tortuous vasculature and the obese patient population. With this in mind we demonstrate how a unique hybridised technique may provide valuable alternative to the neurosciences team should such a future scenario arise.

A computational model for prediction of clot platelet content in flow-diverted intracranial aneurysms.

Treatment of intracranial aneurysms with flow-diverting stents is a safe and minimally invasive technique. The goal is stable embolisation that facilitates stent endothelialisation, and elimination of the aneurysm. However, it is not fully understood why some aneurysms fail to develop a stable clot even with sufficient levels of flow reduction. Computational prediction of thrombus formation dynamics can help predict the post-operative response in such challenging cases. In this work, we propose a new model of thrombus formation and platelet dynamics inside intracranial aneurysms. Our novel contribution combines platelet activation and transport with fibrin generation, which is key to characterising stable and unstable thrombus. The model is based on two types of thrombus inside aneurysms: red thrombus (fibrin- and erythrocyte-rich) can be found in unstable clots, while white thrombus (fibrin- and platelet-rich) can be found in stable clots. The thrombus generation model is coupled to a CFD model and the flow-induced platelet index (FiPi) is defined as a quantitative measure of clot stability. Our model is validated against an in vitro phantom study of two flow-diverting stents with different sizing. We demonstrate that our model accurately predicts the lower thrombus stability in the oversized stent scenario. This opens possibilities for using computational simulations to improve endovascular treatment planning and reduce adverse events, such as delayed haemorrhage of flow-diverted aneurysms.

Mutational analysis of disease relapse in patients allografted for acute myeloid leukemia.

Disease relapse is the major cause of treatment failure after allogeneic stem cell transplantation (allo-SCT) in acute myeloid leukemia (AML). To identify AML-associated genes prognostic of AML relapse post-allo-SCT, we resequenced 35 genes in 113 adults at diagnosis, 49 of whom relapsed. Two hundred sixty-two mutations were detected in 102/113 (90%) patients. An increased risk of relapse was observed in patients with mutations in WT1 (P = .018), DNMT3A (P = .045), FLT3 ITD (P = .071), and TP53 (P = .06), whereas mutations in IDH1 were associated with a reduced risk of disease relapse (P = .018). In 29 patients, we additionally compared mutational profiles in bone marrow at diagnosis and relapse to study changes in clonal structure at relapse. In 13/29 patients, mutational profiles altered at relapse. In 9 patients, mutations present at relapse were not detected at diagnosis. In 15 patients, additional available pre-allo-SCT samples demonstrated that mutations identified posttransplant but not at diagnosis were detectable immediately prior to transplant in 2 of 15 patients. Taken together, these observations, if confirmed in larger studies, have the potential to inform the design of novel strategies to reduce posttransplant relapse highlighting the potential importance of post-allo-SCT interventions with a broad antitumor specificity in contrast to targeted therapies based on mutational profile at diagnosis.

The War on Poverty's Experiment in Public Medicine: Community Health Centers and the Mortality of Older Americans.

This paper uses the rollout of the first Community Health Centers (CHCs) to study the longer-term health effects of increasing access to primary care. Within ten years, CHCs are associated with a reduction in age-adjusted mortality rates of 2 percent among those 50 and older. The implied 7 to 13 percent decrease in one-year mortality risk among beneficiaries amounts to 20 to 40 percent of the 1966 poor/non-poor mortality gap for this age group. Large effects for those 65 and older suggest that increased access to primary care has longer-term benefits, even for populations with near universal health insurance. (JEL H75, I12, I13, I18, I32, I38, J14).

Positioning a proned patient with cauda equina syndrome who presents at 15 weeks gestation: a case report.

Cauda equina syndrome is a neurosurgical emergency that requires prompt intervention to prevent irreversible spinal cord paralysis. This article describes how we managed a case of an obese pregnant patient who was placed in the prone position for surgery. We discuss the evidence behind the management options and choice of operating tables available.

Immunogenicity of DNA- and recombinant protein-based Alzheimer disease epitope vaccines.

Alzheimer disease (AD) process involves the accumulation of amyloid plaques and tau tangles in the brain, nevertheless the attempts at targeting the main culprits, neurotoxic ß-amyloid (Aß) peptides, have thus far proven unsuccessful for improving cognitive function. Important lessons about anti-Aß immunotherapeutic strategies were learned from the first active vaccination clinical trials. AD progression could be safely prevented or delayed if the vaccine (1) induces high titers of antibodies specific to toxic forms of Aß; (2) does not activate the harmful autoreactive T cells that may induce inflammation; (3) is initiated before or at least at the early stages of the accumulation of toxic forms of Aß. Data from the recent passive vaccination trials with bapineuzumab and solanezumab also indicated that anti-Aß immunotherapy might be effective in reduction of the AD pathology and even improvement of cognitive and/or functional performance in patients when administered early in the course of the disease. For the prevention of AD the active immunization strategy may be more desirable than passive immunotherapy protocol and it can offer the potential for sustainable clinical and commercial advantages. Here we discuss the active vaccine approaches, which are still in preclinical development and vaccines that are already in clinical trials.